Manabu Yamamura

Immunohistochemical study of carcinoembryonic antigen in patients with colorectal cancer. Correlation with plasma carcinoembryonic antigen levels

Using peroxidase‐antiperoxidase (PAP) method, carcinoembryonic antigen (CEA) was demonstrated in conventionally processed colorectal cancer tissues. A new immunohistochemical grading for colorectal cancers based on the mode of the localization was made in an attempt to clarify the factors responsible for elevation of plasma CEA levels in colorectal cancer patients. Most of the patients with well differentiated adenocarcinoma, in which CEA was densely distributed along the apical surface but only rarely present along the basolateral surfaces of the carcinoma cells, had very low levels of plasma CEA, whereas all patients showing CEA distribution in the stroma as well as over the entire surfaces of the cancer cells and their cytoplasm showed high plasma CEA levels. In addition, there was a good correlation between the grading and presence of the blood vessel and lymphatic invasions. Thus, the appearance of CEA in the surrounding stroma, due to abnormal distribution of CEA on the basolateral plasma membrane of cancer cells, may play a significant role in the elevation of plasma CEA levels in colorectal cancer patients.

Endocrine cells and prognosis in patients with colorectal carcinoma

Using chromogranin (CG) immunohistochemical staining, the prognostic significance of endocrine differentiation was investigated in 212 patients with primary colorectal adenocarcinoma (including 6 patients with mucosal carcinoma). CG‐immunoreactive cells were found to be an integral component of the tumor in 67 of 206 patients (32.5%, excluding mucosal carcinoma). The intra‐cellular localization of CG in the CG‐immunoreactive cells in cancer tissue was completely different from that in the normal endocrine cells of the large bowel. In addition, morphologic changes such as nuclear hyperchromasia and pleomorphism also indicated that the CG‐immunoreactive cells in the cancer tissue were malignant. The tumors were divided into three groups based on the frequency of CG‐immunoreactive cells: Group I (n = 139), negative; Group II (n = 38), less than 1 positive cell/mm2; and Group III (n = 29), more than 1 positive cell/mm2. No correlation was observed between CG‐immunoreactivity (CG‐IR) and tumor location, grade, depth of invasion, or stage, regardless of lymph node involvement. However, patients with numerous endocrine tumor cells (Group III) had a significantly worse prognosis compared with patients without endocrine cells (Group I) (multivariate Coxs model, P < 0.01). Similar findings were observed in patients with node‐negative tumor (multivariate Coxs model, P < 0.05). These results indicated that the neuroendocrine differentiation is an independent prognostic factor and that CG‐immunohistochemistry is useful for detecting a subgroup with a worse prognosis among patients with colorectal cancer.

Absence of colorectal cancer metastasis to the cirrhotic liver

Hepatic metastasis of colorectal cancer was found in 40 (16%) of 250 patients with colorectal cancer treated in our department during the past 5 years. Liver cirrhosis was not found among the 40 patients with metastases (16%) but was present in 46 (21.9%) of the 210 nonmetastatic patients, with a significant difference between the two groups (p less than 0.001). The rate of patients who were positive for hepatitis B surface antibody was 10% in the metastatic group and 34.3% in the nonmetastatic group, with a significant difference (p less than 0.01). These findings suggest that colorectal cancer does not metastasize to the injured liver, especially the cirrhotic liver.

Effect of Various Lipid Emulsions on Total Parenteral Nutrition-Induced Hepatosteatosis in Rats

The effect of various lipid emulsions on the development of fatty liver during total parenteral nutrition (TPN) was investigated in rats given TPN for 7 days. Medium-chain triglycerides (MCT), long-chain triglycerides (LCT), chemically defined triglycerides (CDT; structured lipid with a high purity of 94.3%), and a mixture of MCT and LCT (MIX) were prepared as the lipid emulsions. TPN provided 350 kcal/kg/day, with a nonprotein calorie/nitrogen ratio of 160. The TPN-1 group received 10% nonprotein calories and the TPN-2 group received 30% nonprotein calories. MCT TPN was found to have some disadvantages, especially with regard to nitrogen balance and plasma albumin levels. Total cholesterol and phospholipids tended to be high in the MCT TPN group. The hepatic lipid content was higher in the lipid-free TPN and the MCT TPN groups, and lower in the CDT and LCT TPN groups. Histologically, the livers of the MIX, CDT, and LCT TPN groups showed less fatty change than those of the FREE and MCT groups.

Clinical Evaluation of a Low Junction of the Cystic Duct

The point of the junction of the cystic duct with the common hepatic duct was studied by means of various preoperative and intraoperative cholangiographic procedures and by gross intraoperative examinations in 468 surgical patients with biliary diseases. The cystic duct entered the hepatic duct at a very low position and was consequently long in 39 patients. The clinical significance of this abnormally low junction of the cystic duct was studied in comparison with 358 patients with gallstones with a normal cystic duct-hepatic duct junction. In the low-junction group with a short common bile duct several complications, including gallstone pancreatitis (7 patients), the Mirizzi syndrome (7), confluence stones (2), gallbladder cancer (3), and congenital dilation of the cystic duct (1), were demonstrated preoperatively. The anomalous junction of the cystic duct with the common bile duct may cause stagnation of bile and/or reflux of pancreatic juice into the bile duct, producing a choledochopancreatic ductal junction and posing difficulties at surgery.

Effect of aprotinin on metastasis of lewis lung tumor in mice

Kallikrein activity in human stomach tissue was measured and found to be about threefold higher in cancer tissue than in normal tissue. To clarify the physiological role of this tissue kallikrein, we investigated its effects on the spontaneous metastasis and tumor growth of Lewis tumors (3LL). Antiprotease, aprotinin, and gabexate mesilate (FOY) inhibited spontaneous metastasis but did not inhibit tumor growth, while tissue kallikrein and plasmin enhanced the spontaneous metastasis of 3LL. The results suggest that the inhibitory effects of aprotinin and FOY on metastasis are not only due to an inhibition of tumor cells released by tissue kallikrein, but that tissue kallikrein, a protease, also participates in metastasis. We thus conclude that aprotinin or FOY should be administered either before or immediately after operation to inhibit spontaneous metastasis.

Carcinoma of the colon in children: Report of a case and review of the literature

Carcinoma of the colon seen in an 11-year-old boy is reported herein. The patient had advanced carcinoma of the ascending colon and died 8 months after an ileo-transversostomy had been performed as a palliative procedure. Histologically, the tumor was found to be signetring cell carcinoma. 29 cases of colon carcinoma reported in Japanese children under 15 years of age are also reviewed. In 19 of these patients, surgery was done as an elective procedure after the diagnosis of colon cancer had been established, but emergency surgery was performed on 10 patients for perforation or obstruction of the bowel. Curative resection was possible in 14 patients, but of these, only 3 patients survived for more than 10 years.

Effect of medium-chain triglycerides (MCT) as an energy substrate after hepatectomy in rats with streptozotocin-induced diabetes

SummaryThe suitability of energy substrates used by the remnant liver after a 70% partial hepatectomy was studied in relation to the hepatic energy status in diabetic rats. Rats with streptozotocin-induced diabetes mellitus underwent 70% hepatectomy, and were divided into three groups receiving total parenteral nutrition (TPN) for 24h. One group received standard TPN without fat, while two other groups received standard TPN with medium-chain triglycerides (MCTs) or long-chain triglycerides (LCTs) as a 10% lipid emulsion. All rats of the TPN group without fat died within 24 h. Blood ketone body ratios (acetoacetate/β-hydroxybutyrate), energy charge levels of the remnant liver, and cumulative amounts of 14CO2 in the expired breath during the 6 h following 14C-labeled fat emulsion administration (MCT or LCT) were all significantly higher in the MCT group than in the LCT group 24 h after hepatectomy. These findings suggest that medium-chain fatty acids (MCFAs) as an energy substrate are superior to long-chain fatty acids (LCFAs) during the immediate posthepatectomy phase in diabetics.

Postoperative immunization with peanut agglutinin-binding glycoprotein from Lewis lung carcinoma in mice

The effects of postoperative immunization with purified tumor-associated antigens on the development of lung metastases following excision of the Lewis lung carcinoma (3LL) were investigated. Soluble tumor-associated antigens were isolated from 3LL cells by detergent solubilization and purified by affinity chromatography on peanut agglutinin (PNA)-agarose. The immunization with subcutaneous injections of PNA-binding glycoproteins (PNA receptors) at the early phase following excision of primary footpad tumors of 3LL resulted in a significant decrease in incidence and size of lung metastases. The delayed immunization, however, failed to suppress the development and growth of metastatic lung tumors after surgery. The suppression in postoperative development of lung metastases was found to depend on the scheduling of immunization following local tumor excision. Splenectomy performed simultaneously with amputation of the tumor-bearing leg completely abolished the decrease in the development and growth of postoperative lung metastases in immunized mice. The involvement of the lymphoid system in the control of metastatic tumor growth was also confirmed in an in vivo tumor neutralization assay utilizing the spleen cells.

Effects of Eicosapentaenoic Acid on Lipid Metabolism in Obesity Treatment.

In this study, we investigated the hypolipidemic action of eicosapentaenoic acid (EPA) and its mechanism. Three types of 5% fat diets (stearic acid, linoleic acid, and EPA) were prepared in our laboratory. Rats that weighed 170-190 g were fed one of these diets for 20 weeks at an equivalent calorie value (groups S, L, and E). Weight gain occurred in the following order: group E < group S < group L. Serum levels of total cholesterol, triglycerides, phospholipids and total lipids were significantly lower in group E than in the other groups. Analysis of the fatty acid composition of adipose tissue showed that the level of C18:1 was significantly higher in group S, that of C18:2 was significantly higher in group L, and that of C16:0 was significantly higher in group E than in the other groups. Arterial ketone bodies were significantly higher in group E than in the other groups. These results indicated that EPA had a hypolipidemic action, higher ketogenicity, and lower lipogenicity than the other fatty acids. Inclusion of EPA in the diet of hyperlipidemic subjects may thus help in the primary prevention of hyperlipidemia and, in turn, morbid obesity.